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Amoud medical school
Dr. Mukhtar Jama Nour , MBBS, MD
METABOLIC
PATHWAYS
CATABOLICPATHWAYS
Are involved in oxidative
breakdown of larger
complexes.
They are usually
exergonic in nature
ANABOLIC PATHWAYS
Are involved in the
synthesis of
compounds.
They are usually
endergonic in nature.
CHARACTERISTICS OF METABOLISM
1. Metabolic pathways are mostly irreversible
2. Every metabolic pathway has a committed
first step.
3. All metabolic pathways are regulated.
4. Metabolic pathways in eukaryotic cells occur
in specific cellular locations.
GLYCOLYSIS
Glycolysis comes from a merger of two Greek words:
Glykys = sweet
Lysis = breakdown/ splitting
It is also known as Embden-Meyerhof-Parnas pathway
or EMP pathway.
INTRODUCTION
• GLYCOLYSIS is the sequence of 10 enzyme-catalyzed
reactions that converts glucose into pyruvate with
simultaneous production on of ATP.
• In this oxidative process, 1mol of glucose is partially
oxidised to 2 moles of pyruvate.
• This major pathway of glucose metabolism occurs in
the cytosol of all cell.
• This unique pathway occurs aerobically as well as
anaerobically & doesn’t involve molecular oxygen.
• It also includes formation of Lactate from Pyruvate.
• The glycolytic sequence of reactions differ from
species to species only in the mechanism of its
regulation & in the subsequent metabolic fate of
the pyruvate formed.
• In aerobic organisms, glycolysis is the prelude to
Citric acid cycle and ETC.
• Glycolysis is the central pathway for Glucose
catabolism.
Glucose
Extracellular
matrix & cell wall
polysachharide.
Glycogen,
Starch,
Sucrose
Pyruvate
Ribose-5-
phosphat
e
Oxidation via
pentose phosphate
pathway
Synthesis of
structural polymers
storage
Oxidation
via glycolysis
Major pathways of
glucose utilization.
TWO PHASES OF GLYCOLYSIS
• Glycolysis leads to breakdown of 6-C glucose
into two molecules of 3-C pyruvate with the
enzyme catalyzed reactions being bifurcated
or categorized into 2 phases:
1. Phase 1- preparatory phase
2. Phase 2- payoff phase.
PREPARATORY PHASE
• It consists of the 1st 5 steps of glycolysis in which
the glucose is enzymatically phosphorylated by ATP
to yield Fructose-1,6-biphosphate.
• This fructuse-1,6-biphosphate is then split in half to
yield 2 molecules of 3-carbon containing
Glyceraldehyde-3-phosphate/ dihyroxyacteone
phosphate.
• Thus the first phase results in cleavage of the
hexose chain.
• This cleavage requires an investment of 2 ATP
molecules to activate the glucose mole and prepare
it for its cleavage into 3-carbon compound.
PAYOFF PHASE
• This phase constitutes the last 5 reactions of
Glycolysis.
• This phase marks the release of ATP molecules
during conversion of Glyceraldehyde-3-phosphtae
to 2 moles of Pyruvate.
• Here 4 moles of ADP are phosphorylated to ATP.
Although 4 moles of ATP are formed, the net result
is only 2 moles of ATP per mole of Glucose oxidized,
since 2 moles of ATP are utilized in Phase 1.
STEPWISE EXPLANATION OF
GLYCOLYSIS
STEP 1: PHOSPHORYLATION
• Glucose is phosphorylated by ATP to form sugar
phosphate.
• This is an irreversible reaction & is catalyzed by
hexokinase.
• Thus the reaction can be represented as follows:
Glucose
Glucose-6-phosphate
Hexokinase
ATP
ADP
STEP 2: ISOMERIZATION
• It is a reversible rearrangement of chemical structure of
carbonyl oxygen from C1 to C2, forming a Ketose from the
Aldose.
• Thus, isomerization of the aldose Glucose6-phosphate
gives the ketose, Fructose-6-phoshphate.
Glucose-6-phosphate
Phosphoglucoisomerase
Fructose-6-phosphate
STEP 3: PHOPHORYLATION
• Here the Fructose-6-phosphate is phosphorylated
by ATP to fructose-1,6-bisphosphate.
• This is an irreversible reaction and is catalyzed by
phosphofructokinase enzyme.
Fructose-6-phosphate
Fructose-1,6-bisphosphate
ATP
ADP
Phosphofructokinase
STEP 4: BREAKDOWN
• This six carbon sugar is cleaved to produce two 3-C
molecules: glyceradldehyde-3-phosphate (GAP) &
dihydroxyacetone phosphate(DHAP).
• This reaction is catalyzed by Aldolase.
Glyceraldehyde-3-
phosphate
Dihydroxyacetone
phosphate
Triose phosphate
isomerase
Fructose-1,6-
bisphosphate
Aldolase
STEP 5: ISOMERIZATION
• Dihydroxyacetone phosphate is oxidized to form
Glyceraldehyde-3-phosphate.
• This reaction is catalyzed by triose phosphate
isomerase enzyme.
Glyceraldehyde-3-phosphate
Dihydroxyacetone phosphate
Triose phosphate
isomerase
2
2
STEP 6
• 2 molecules of Glyceraldehyde-3-phosphate are
oxidized.
• Glyceraldehyde-3-phosphate dehydrogenase
catalyzes the conversion of Glyceraldehyde3-
phosphate into 1,3-bisphosphoglycerate.
Resultant reaction
Glyceraldehyde-3-phosphate
1,3-bisphosphoglycerate
Glyceraldehyde-3-phosphate
dehydrogenase
2NAD⁺ + 2Pi
2NADH + 2H⁺
2
2
STEP 7
• The transfer of high-energy phosphate group that
was generated earlier to ADP, form ATP.
• This phosphorylation i.e. addition of phosphate to
ADP to give ATP is termed as substrate level
phosphorylation as the phosphate donor is the
substrate 1,3-bisphosphoglycerate (1,3-BPG).
• The product of this reaction is 2 molecules of
3-phosphoglycerate.
1,3-bisphosphoglycerate
3-phosphoglycerate
Phosphoglycerate
kinase 2 ADP
2 ATP
FIRST SUBSTRATE LEVEL
PHOSPHORYLATION
2
2
STEP 8
• The remaining phosphate-ester linkage in 3-
phosphoglycerate, is moved from carbon 3 to
carbon 2 ,because of relatively low free energy of
hydrolysis, to form 2-phosphoglycerate(2-PG).
3-phosphoglycerate
2-phosphoglycerate
Phosphoglycerate
mutase
2
2
STEP 9: DEHYDRATION OF 2-PG
• This is the second reaction in glycolysis where a
high-energy phosphate compound is formed.
• The 2-phosphoglycerate is dehydrated by the action
of enolase to phosphoenolpyruvate(PEP). This
compound is the phosphate ester of the enol
tautomer of pyruvate.
• This is a reversible reaction.
2-phosphoglycerate
Phosphoenol pyruvate
H₂O
Enolase
2
2
STEP 10: TRANSFER OF PHOSPHATE
FROM PEP to ADP
• This last step is the irreversible transfer of high
energy phosphoryl group from
phosphoenolpuruvate to ADP.
• This reaction is catalyzed by pyruvate kinase.
• This is the 2nd substrate levelphosphorylation
reaction in glycolysis which yields ATP.
Phosphoenolpyruvate
Pyruvate
2
2
Pyruvate kinase
SECOND
SUBSTRATE LEVEL
PHOSPHORYLATION
2ADP
2ATP
OVERALL BALANCE SHEET OF
GLYCOLYSIS
• Each molecule of glucose gives 2 molecules of
Glyceraldehyde-3-phosphate. Therefore , the total
input of all 10 reactions can be summarized as:
Glucose + 2ATP+ 2Pi+ 2NAD⁺+ 2H⁺+ 4ADP
2Pyruvate+ 2H⁺+ 4ATP+ 2H₂O+ 2NADH+ 2ADP
On cancelling the common terms from the above
equation, we get the net equation for Glycolysis:
Glucose+ 2Pi+ 2ADP+ 2NAD⁺
2Pyruvate+ 2NADH+ 2ATP+ 2H⁺ + 2H₂O
THUS THE SIMULTANEOUS REACTIONS INVOLVED IN
GLYCOLYSIS ARE:
Glucose is oxidized to Pyruvate
NAD⁺ is reduced to NADH
ADP is phosphorylated to ATP
• ENERGY YIELD IN GLYCOLYSIS:
STEP NO. REACTION CONSUMPTION of ATP GAIN of ATP
1 1 -
3
Glucose glucose-6-phosphate
Fructose-6-phosphate
fructose-1,6-biphosphate
1 -
7 - 1x2=2
10
1,3-diphosphoglycerate
3-phosphoglycerate
Phosphoenolpyruvate pyruvate - 1x2=2
2 4
Net gain of ATP=4-2= 2
glycolysis jhoinnbhvtftdtdtcftftfttctctctctct

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  • 1. Amoud medical school Dr. Mukhtar Jama Nour , MBBS, MD
  • 2. METABOLIC PATHWAYS CATABOLICPATHWAYS Are involved in oxidative breakdown of larger complexes. They are usually exergonic in nature ANABOLIC PATHWAYS Are involved in the synthesis of compounds. They are usually endergonic in nature.
  • 3. CHARACTERISTICS OF METABOLISM 1. Metabolic pathways are mostly irreversible 2. Every metabolic pathway has a committed first step. 3. All metabolic pathways are regulated. 4. Metabolic pathways in eukaryotic cells occur in specific cellular locations.
  • 4.
  • 5. GLYCOLYSIS Glycolysis comes from a merger of two Greek words: Glykys = sweet Lysis = breakdown/ splitting It is also known as Embden-Meyerhof-Parnas pathway or EMP pathway.
  • 6. INTRODUCTION • GLYCOLYSIS is the sequence of 10 enzyme-catalyzed reactions that converts glucose into pyruvate with simultaneous production on of ATP. • In this oxidative process, 1mol of glucose is partially oxidised to 2 moles of pyruvate. • This major pathway of glucose metabolism occurs in the cytosol of all cell. • This unique pathway occurs aerobically as well as anaerobically & doesn’t involve molecular oxygen.
  • 7. • It also includes formation of Lactate from Pyruvate. • The glycolytic sequence of reactions differ from species to species only in the mechanism of its regulation & in the subsequent metabolic fate of the pyruvate formed. • In aerobic organisms, glycolysis is the prelude to Citric acid cycle and ETC. • Glycolysis is the central pathway for Glucose catabolism.
  • 8. Glucose Extracellular matrix & cell wall polysachharide. Glycogen, Starch, Sucrose Pyruvate Ribose-5- phosphat e Oxidation via pentose phosphate pathway Synthesis of structural polymers storage Oxidation via glycolysis Major pathways of glucose utilization.
  • 9.
  • 10. TWO PHASES OF GLYCOLYSIS • Glycolysis leads to breakdown of 6-C glucose into two molecules of 3-C pyruvate with the enzyme catalyzed reactions being bifurcated or categorized into 2 phases: 1. Phase 1- preparatory phase 2. Phase 2- payoff phase.
  • 11. PREPARATORY PHASE • It consists of the 1st 5 steps of glycolysis in which the glucose is enzymatically phosphorylated by ATP to yield Fructose-1,6-biphosphate. • This fructuse-1,6-biphosphate is then split in half to yield 2 molecules of 3-carbon containing Glyceraldehyde-3-phosphate/ dihyroxyacteone phosphate.
  • 12. • Thus the first phase results in cleavage of the hexose chain. • This cleavage requires an investment of 2 ATP molecules to activate the glucose mole and prepare it for its cleavage into 3-carbon compound.
  • 13.
  • 14. PAYOFF PHASE • This phase constitutes the last 5 reactions of Glycolysis. • This phase marks the release of ATP molecules during conversion of Glyceraldehyde-3-phosphtae to 2 moles of Pyruvate. • Here 4 moles of ADP are phosphorylated to ATP. Although 4 moles of ATP are formed, the net result is only 2 moles of ATP per mole of Glucose oxidized, since 2 moles of ATP are utilized in Phase 1.
  • 15.
  • 17. STEP 1: PHOSPHORYLATION • Glucose is phosphorylated by ATP to form sugar phosphate. • This is an irreversible reaction & is catalyzed by hexokinase. • Thus the reaction can be represented as follows: Glucose Glucose-6-phosphate Hexokinase ATP ADP
  • 18. STEP 2: ISOMERIZATION • It is a reversible rearrangement of chemical structure of carbonyl oxygen from C1 to C2, forming a Ketose from the Aldose. • Thus, isomerization of the aldose Glucose6-phosphate gives the ketose, Fructose-6-phoshphate. Glucose-6-phosphate Phosphoglucoisomerase Fructose-6-phosphate
  • 19. STEP 3: PHOPHORYLATION • Here the Fructose-6-phosphate is phosphorylated by ATP to fructose-1,6-bisphosphate. • This is an irreversible reaction and is catalyzed by phosphofructokinase enzyme. Fructose-6-phosphate Fructose-1,6-bisphosphate ATP ADP Phosphofructokinase
  • 20. STEP 4: BREAKDOWN • This six carbon sugar is cleaved to produce two 3-C molecules: glyceradldehyde-3-phosphate (GAP) & dihydroxyacetone phosphate(DHAP). • This reaction is catalyzed by Aldolase. Glyceraldehyde-3- phosphate Dihydroxyacetone phosphate Triose phosphate isomerase Fructose-1,6- bisphosphate Aldolase
  • 21. STEP 5: ISOMERIZATION • Dihydroxyacetone phosphate is oxidized to form Glyceraldehyde-3-phosphate. • This reaction is catalyzed by triose phosphate isomerase enzyme. Glyceraldehyde-3-phosphate Dihydroxyacetone phosphate Triose phosphate isomerase 2 2
  • 22. STEP 6 • 2 molecules of Glyceraldehyde-3-phosphate are oxidized. • Glyceraldehyde-3-phosphate dehydrogenase catalyzes the conversion of Glyceraldehyde3- phosphate into 1,3-bisphosphoglycerate.
  • 24. STEP 7 • The transfer of high-energy phosphate group that was generated earlier to ADP, form ATP. • This phosphorylation i.e. addition of phosphate to ADP to give ATP is termed as substrate level phosphorylation as the phosphate donor is the substrate 1,3-bisphosphoglycerate (1,3-BPG). • The product of this reaction is 2 molecules of 3-phosphoglycerate.
  • 25. 1,3-bisphosphoglycerate 3-phosphoglycerate Phosphoglycerate kinase 2 ADP 2 ATP FIRST SUBSTRATE LEVEL PHOSPHORYLATION 2 2
  • 26. STEP 8 • The remaining phosphate-ester linkage in 3- phosphoglycerate, is moved from carbon 3 to carbon 2 ,because of relatively low free energy of hydrolysis, to form 2-phosphoglycerate(2-PG). 3-phosphoglycerate 2-phosphoglycerate Phosphoglycerate mutase 2 2
  • 27. STEP 9: DEHYDRATION OF 2-PG • This is the second reaction in glycolysis where a high-energy phosphate compound is formed. • The 2-phosphoglycerate is dehydrated by the action of enolase to phosphoenolpyruvate(PEP). This compound is the phosphate ester of the enol tautomer of pyruvate. • This is a reversible reaction.
  • 29. STEP 10: TRANSFER OF PHOSPHATE FROM PEP to ADP • This last step is the irreversible transfer of high energy phosphoryl group from phosphoenolpuruvate to ADP. • This reaction is catalyzed by pyruvate kinase. • This is the 2nd substrate levelphosphorylation reaction in glycolysis which yields ATP.
  • 31. OVERALL BALANCE SHEET OF GLYCOLYSIS • Each molecule of glucose gives 2 molecules of Glyceraldehyde-3-phosphate. Therefore , the total input of all 10 reactions can be summarized as: Glucose + 2ATP+ 2Pi+ 2NAD⁺+ 2H⁺+ 4ADP 2Pyruvate+ 2H⁺+ 4ATP+ 2H₂O+ 2NADH+ 2ADP On cancelling the common terms from the above equation, we get the net equation for Glycolysis:
  • 32. Glucose+ 2Pi+ 2ADP+ 2NAD⁺ 2Pyruvate+ 2NADH+ 2ATP+ 2H⁺ + 2H₂O THUS THE SIMULTANEOUS REACTIONS INVOLVED IN GLYCOLYSIS ARE: Glucose is oxidized to Pyruvate NAD⁺ is reduced to NADH ADP is phosphorylated to ATP
  • 33. • ENERGY YIELD IN GLYCOLYSIS: STEP NO. REACTION CONSUMPTION of ATP GAIN of ATP 1 1 - 3 Glucose glucose-6-phosphate Fructose-6-phosphate fructose-1,6-biphosphate 1 - 7 - 1x2=2 10 1,3-diphosphoglycerate 3-phosphoglycerate Phosphoenolpyruvate pyruvate - 1x2=2 2 4 Net gain of ATP=4-2= 2